Mechanisms of neutrophil extravasation in microcirculation.

A series of the process of neutrophil extravasation induced by topical application of leukotriene B4 (LTB4) or formyl-methionyl-leucyl-phenylalanine (fMLP) on microvasculature of the hamster cheek pouch can be divided into five steps; I) rolling on the venular endothelium, II) adhesion on the endothelium, III) passage between the endothelial cells, IV) staying in the venular wall, V) migration from the venular wall to the interstitial space. In step II, topical application of chemoattractants on the microvasculature caused an increase in the number of neutrophils adhered to the venules. In step III, the size of the adhered neutrophils became gradually smaller and finallly disappear from the vascular lumen, as they were observed on the monitor screen. Over 80-90% of the adhered neutrophils passed through the endothelial cells. The whole process from step II to III took about 7 minutes. In step IV, the neutrophils which passed through the endothelial cells stay for about 30 minutes in the venular wall. In step V, neutrophils penetrated the basement membrane and migrated into the interstitial space.Step II and III were suppressed by a cyclic AMP phosphodiesterase inhibitor, fibronectin inhibitor and cytochalasin B. From these results, it was suggested that chemoattractant may cause the contraction of microfilament of neutrophil, and the contraction may induce the expression of adhesive glycoprotein on the neutrophil membrane. The increase of cyclic AMP in the neutrophil may inhibit the contraction of microfilament and/or the expression of adhesive glycoprotein of neutrophil. Dexamethasone did not affect the step I to IV, but suppressed the step V. Dexamethasone may inhibit synthesis and/or release of protease (s) in the neutrophil granules which degrade the basement membrane. In fact, the collagenase inhibitor suppressed the step V, although it did not the step I to IV. Thus, neutophil-derived collagenase may act on the passage of neutrophil through the basement membrane. The process of neutrophil extravasation is the chain of reaction.